Evaluation of the Effect of Gabexate Mesilate in the Hepatocyte Protection After Liver Resection
Status:
Terminated
Trial end date:
2017-02-25
Target enrollment:
Participant gender:
Summary
Liver resection have been a primary treatment option for lesions found in the liver. With
improvements in surgical technique and perioperative patient management, morbidity and
mortality related to liver resection have been greatly reduced. However, many patients with
hepatocellular carcinoma have underlying liver disease. Severity of underlying liver disease
plays an important role in decision making of resection extent. Therefore, liver failure and
decreased liver function following liver resection still remains to be an critical issue.
Postresection liver failure is generally defined by serum total bilirubin greater than 3mg/dL
and prothrombin time of less than 50% of normal (INR >1.7). Pathophysiology of postresection
liver failure is not yet well known. However, sepsis after liver resection, small-for-size
syndrome (SFSS), and ischemia/reperfusion injury are known to have important roles in
persistant liver injury after resection.
After a liver resection, kupffer cells are drastically decreased and innate immunity of the
patient is also damaged. This process causes the patient to be vulnerable to infection. In
addition, with continuous endotoxin secretion, dysfunction in kupffer cells are triggered and
liver regeneration is affected.
Complex mechanisms leading to dysfunctional kupffer cells and apoptosis and necrosis of
hepatocytes are mediated by neutrophils, complement, reactive oxygen species, and acute
inflammatory cytokines.
Recent studies have reported on many promising effects of the synthetic protease inhibitor,
such as Gabexate mesilate. These include antioxidant effect, inhibition of acute inflammatory
cytokine reaction, and anticoagulatory property. Based on these effects, synthetic protease
inhibitor have gained attention in the role of hepatocyte protection after liver resection.
Currently, there is a report on the hepatocyte protective effects of Gabexate Mesilate on
ischemia/reperfusion injury caused by the Pringle maneuver. However, with the advances in
surgical technique and equipment, many surgeons now perform liver resection without Pringle
maneuver. Therefore, this study was designed to determine effects of Gabexate Mesilate in the
liver resection performed without Pringle maneuver.